The present invention relates to novel specifically-substituted phenyl compounds, especially substituted tert-butylphenol compounds, which are effective as anti-inflammatory, analgesic and/or antipyretic agents. The present invention further relates to pharmaceutical compositions which are useful for treating diseases which involve inflammation, pain, and/or fever. Finally, the present invention relates to methods for treating diseases characterized by inflammation.
The search for new non-steroidal anti-inflammatory ("NSAI") drugs over the last 10 to 20 years has led to the testing by various researchers and companies of thousands of compounds for efficacy as anti-inflammatories. The search has raised many questions, but provided few answers, about how and why some compounds are efficacious and others are not, especially for substituted tert-butylphenol compounds. This search, and the results and questions raised thereby, are discussed more fully in "Anti-inflammatory Activity of Anti-oxidants", by K. F. Swingle, et al., Chapter 4 of Anti-inflammatory and Anti-rheumatic Drugs, Vol. III (K. D. Rainsford, Editor; CRC Press, Inc.; 1985), pages 105-126, which is incorporated herein by reference.
Notwithstanding the great effort already put forth to identify NSAI drugs, there remains a continuing need to identify new compounds and compositions which are effective for treating inflammation and inflammatory diseases such as rheumatoid arthritis and osteoarthritis. It is accordingly an object of the present invention to provide compounds which are effective anti-inflammatory agents, as well as pharmaceutical compositions containing these compounds. It is a further object of the present invention to provide methods for treating diseases characterized by inflammation.
It is a further object of the present invention to provide compounds which have one or more of the following uses: anti-inflammatory agents, analgesic agents, antipyretic agents, antioxidant agents, antiarthritic agents, bone modifying agents, immunomodulating agents, antilipidemic agents, antiresorptive agents or agents for reversing ischaemia-induced cell damage; and pharmaceutical compositions containing these compounds. A still further object of the present invention is to provide compounds, and compositions containing these compounds, which have high efficacy, low toxicity (such as low gastrointestinal irritability), prolonged duration of action, and/or good therapeutic indices.
These and other objects wil become readily apparent from the detailed description which follows.